Effect of 15-HETE on cerebral arterioles of newborn pigs

Effects of topical application of 15-HETE on pial arteriolar diameter and cortical periarachnoid cerebrospinal fluid (CSF) prostanoid concentrations were investigated in chloralose-anesthetized newborn pigs. Pial arteriolar diameters were measured using a closed cranial window, and CSF samples from under the window were collected for prostanoid analysis after applying artificial CSF without drug and CSF containing 15-HETE (1, 10, 100, 10000 ng/ml). 15-HETE caused significant dose-related constriction from 162 +/- 17.0 microns (control diameter) to 136 +/- 14.5 and 129 +/- 18.7 microns (100 and 1000 ng/ml, respectively). The concentration of PGE2 (but not of PGF2 alpha or 6-keto-PGF1 alpha) increased in CSF at 100 and 1000 ng/ml of 15-HETE. Pial arteriolar responses to 15-HETE were determined before and after indomethacin treatment (5 mg/kg, i.v.). 15-HETE (100 ng/ml) constricted pial arterioles before indomethacin (diameter change, -15 +/- 10%); after indomethacin, constriction was potentiated in response to the same dose (diameter change, -26 +/- 7%). These data support the hypothesis that, in newborn piglets, 15-HETE exerts a vasoconstrictor effect on pial arterioles, which appears to be attenuated by 15-HETE-induced stimulation of dilator prostanoids.